ORIENTAL: Orantinib In Combination With Transcatheter Arterial Chemoembolization In Patients With Unresectable Hepatocellular Carcinoma
Sponsor
Taiho Pharmaceutical Co., Ltd. (Industry)
Overall Status
Terminated
CT.gov ID
NCT01465464
Collaborator
(none)
888
6
2
47
148
3.1
Study Details
Study Description
Brief Summary
The purpose of this study is to compare the overall survival (OS) for Orantinib in combination with transcatheter arterial chemoembolization (TACE) versus placebo in combination with TACE in patients with unresectable hepatocellular carcinoma (HCC).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This is a randomized, multi-center, double-blind, placebo-controlled phase III trial of Orantinib administered in combination with TACE in patients with unresectable HCC.
Patients will be randomly assigned (1:1) to receive TACE given in combination with either Orantinib (200 mg orally, twice per day) or placebo.
ORIENTAL:ORantinib InvEstigatioN on TAce combination triaL.
Study Design
Study Type:
Interventional
Actual Enrollment
:
888 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Placebo-Controlled Phase III Trial Of TSU-68 In Combination With Transcatheter Arterial Chemoembolization In Patients With Unresectable Hepatocellular Carcinoma
Study Start Date
:
Dec 1, 2010
Actual Primary Completion Date
:
Jun 1, 2014
Actual Study Completion Date
:
Nov 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Orantinib
|
Drug: Orantinib (TSU-68)
200 mg (1 tablet) of Orantinib was administered orally twice per day after meals, morning and evening.
|
| Placebo Comparator: Placebo
|
Drug: Placebo
1 tablet was administered orally twice per day after meals, morning and evening.
|
Outcome Measures
Primary Outcome Measures
- Overall Survival(OS) [The time from the date of enrollment to the date of death from any cause, assessed up to three years after randomizationof the last patient]
Secondary Outcome Measures
- Time to Transcatheter Arterial Chemoembolization (TACE) Failure [The time from the date of enrollment to the date of event for TACE discontinuation, assessed up to three years after randomizationof the last patient]
Patients should not receive additional TACE therapy in this study after meeting any of the following conditions, at the Investigator's discretion. The patient develops an intra-hepatic lesion that is uncontrolled by serial TACE Deterioration in arterial pathways to treat HCC that makes additional TACE impossible Severe vascular invasion occurs that makes additional TACE impossible Extra hepatic spread considered relevant to life expectancy that requires another treatment modality for HCC Liver function at grade Child-Pugh class C lasting for 28 days
Eligibility Criteria
Criteria
Ages Eligible for Study:
20 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Patients must be diagnosed as HCC.
-
Patients has no indications for treatment with curative hepatic resection or curative percutaneous local therapy.
-
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
-
Patients are able to receive oral medication.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Local Institution | Osaka-sayama | Osaka | Japan | 589-8511 |
| 2 | Local Institution | Chuo-ku | Tokyo | Japan | 104-0045 |
| 3 | Local Institution | Chiba | Japan | 260-8677 | |
| 4 | Local Institution | Goyang-si | Gyeonggi-do | Korea, Republic of | 410-769 |
| 5 | Local Institution | Seoul | Korea, Republic of | 110-744 | |
| 6 | Local Institution | Taipei | Taiwan | 100 |
Sponsors and Collaborators
- Taiho Pharmaceutical Co., Ltd.
Investigators
- Study Director: Taiho Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Taiho Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01465464
Other Study ID Numbers:
- Taiho132150
First Posted:
Nov 4, 2011
Last Update Posted:
Aug 7, 2019
Last Verified:
Aug 1, 2019
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Orantinib | Placebo |
|---|---|---|
| Arm/Group Description | Orantinib (TSU-68): 200 mg (1 tablet) of Orantinib was administered orally twice per day after meals, morning and evening. | Placebo: 1 tablet was administered orally twice per day after meals, morning and evening. |
| Period Title: Overall Study | ||
| STARTED | 444 | 444 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 444 | 444 |
Baseline Characteristics
| Arm/Group Title | Orantinib | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Orantinib (TSU-68): 200 mg (1 tablet) of Orantinib was administered orally twice per day after meals, morning and evening. | Placebo: 1 tablet was administered orally twice per day after meals, morning and evening. | Total of all reporting groups |
| Overall Participants | 444 | 444 | 888 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
189
42.6%
|
202
45.5%
|
391
44%
|
| >=65 years |
255
57.4%
|
242
54.5%
|
497
56%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
81
18.2%
|
80
18%
|
161
18.1%
|
| Male |
363
81.8%
|
364
82%
|
727
81.9%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
444
100%
|
444
100%
|
888
100%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| White |
0
0%
|
0
0%
|
0
0%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| South Korea |
170
38.3%
|
170
38.3%
|
340
38.3%
|
| Japan |
219
49.3%
|
213
48%
|
432
48.6%
|
| Taiwan |
55
12.4%
|
61
13.7%
|
116
13.1%
|
Outcome Measures
| Title | Overall Survival(OS) |
|---|---|
| Description | |
| Time Frame | The time from the date of enrollment to the date of death from any cause, assessed up to three years after randomizationof the last patient |
Outcome Measure Data
| Analysis Population Description |
|---|
| When approximately 50% of the targeted number of time to TACE discontinuation events were confirmed, interim analysis was performed by IDMC. Because the Committee considered that significant results would no longer be obtained, the IDMC recommended to the Sponsor that the clinical trial would be discontinued, and the Sponsor stopped this trial. |
| Arm/Group Title | Orantinib | Placebo |
|---|---|---|
| Arm/Group Description | Orantinib (TSU-68): 200 mg (1 tablet) of Orantinib was administered orally twice per day after meals, morning and evening. | Placebo: 1 tablet was administered orally twice per day after meals, morning and evening. |
| Measure Participants | 168 | 163 |
| Median (95% Confidence Interval) [days] |
946.0
|
984.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.435 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.090 | |
| Confidence Interval |
(2-Sided) 95% 0.878 to 1.352 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Transcatheter Arterial Chemoembolization (TACE) Failure |
|---|---|
| Description | Patients should not receive additional TACE therapy in this study after meeting any of the following conditions, at the Investigator's discretion. The patient develops an intra-hepatic lesion that is uncontrolled by serial TACE Deterioration in arterial pathways to treat HCC that makes additional TACE impossible Severe vascular invasion occurs that makes additional TACE impossible Extra hepatic spread considered relevant to life expectancy that requires another treatment modality for HCC Liver function at grade Child-Pugh class C lasting for 28 days |
| Time Frame | The time from the date of enrollment to the date of event for TACE discontinuation, assessed up to three years after randomizationof the last patient |
Outcome Measure Data
| Analysis Population Description |
|---|
| When approximately 50% of the targeted number of time to TACE discontinuation events were confirmed, interim analysis was performed by IDMC. Because the Committee considered that significant results would no longer be obtained, the IDMC recommended to the Sponsor that the clinical trial would be discontinued, and the Sponsor stopped this trial. |
| Arm/Group Title | Orantinib | Placebo |
|---|---|---|
| Arm/Group Description | Orantinib (TSU-68): 200 mg (1 tablet) of Orantinib was administered orally twice per day after meals, morning and evening. | Placebo: 1 tablet was administered orally twice per day after meals, morning and evening. |
| Measure Participants | 174 | 206 |
| Median (95% Confidence Interval) [days] |
728.0
|
602.0
|
Adverse Events
| Time Frame | From the date of the first treatment to 30 days after the last treatment | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Main treatment discontinuation criteria The Investigator concludes that the patients should be treated with another treatment modality except TACE for HCC Patient has unacceptable/intolerable toxicities Patient can not take both enhanced CT and enhanced MRI of the abdomen any more Patient wishes to discontinue the treatment | |||
| Arm/Group Title | Orantinib | Placebo | ||
| Arm/Group Description | Orantinib (TSU-68): 200 mg (1 tablet) of Orantinib was administered orally twice per day after meals, morning and evening. | Placebo: 1 tablet was administered orally twice per day after meals, morning and evening. | ||
All Cause Mortality |
||||
| Orantinib | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 33/444 (7.4%) | 24/444 (5.4%) | ||
Serious Adverse Events |
||||
| Orantinib | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 200/444 (45%) | 134/444 (30.2%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 3/444 (0.7%) | 0/444 (0%) | ||
| Disseminated intravascular coagulation | 2/444 (0.5%) | 0/444 (0%) | ||
| Leukocytosis | 1/444 (0.2%) | 0/444 (0%) | ||
| Idiopathic thrombocytopenic purpura | 0/444 (0%) | 1/444 (0.2%) | ||
| Cardiac disorders | ||||
| Acute pericarditis | 1/444 (0.2%) | 0/444 (0%) | ||
| Angina pectoris | 1/444 (0.2%) | 0/444 (0%) | ||
| Atrial thrombosis | 1/444 (0.2%) | 0/444 (0%) | ||
| Cardiopulmonary arrest | 1/444 (0.2%) | 0/444 (0%) | ||
| Heart failure | 1/444 (0.2%) | 0/444 (0%) | ||
| Left ventricular dysfunction | 1/444 (0.2%) | 0/444 (0%) | ||
| Myocardial infarction | 3/444 (0.7%) | 0/444 (0%) | ||
| Paroxysmal supraventricular tachycardia | 1/444 (0.2%) | 0/444 (0%) | ||
| Pericardial effusion | 1/444 (0.2%) | 0/444 (0%) | ||
| Acute myocardial infarction | 0/444 (0%) | 1/444 (0.2%) | ||
| Congenital, familial and genetic disorders | ||||
| Hydrocele cord | 1/444 (0.2%) | 0/444 (0%) | ||
| Endocrine disorders | ||||
| Hypothyroidism | 0/444 (0%) | 1/444 (0.2%) | ||
| Eye disorders | ||||
| Cataract | 4/444 (0.9%) | 3/444 (0.7%) | ||
| Cataract aggravated | 3/444 (0.7%) | 1/444 (0.2%) | ||
| Diabetic retinopathy | 0/444 (0%) | 1/444 (0.2%) | ||
| Retinal macroaneurysm | 0/444 (0%) | 1/444 (0.2%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 9/444 (2%) | 7/444 (1.6%) | ||
| Acute pancreatitis | 1/444 (0.2%) | 0/444 (0%) | ||
| Anal fistula | 1/444 (0.2%) | 0/444 (0%) | ||
| Acute gastric ulcer with haemorrhage | 0/444 (0%) | 1/444 (0.2%) | ||
| Ascites | 19/444 (4.3%) | 11/444 (2.5%) | ||
| Colonic polyp | 1/444 (0.2%) | 0/444 (0%) | ||
| Dental caries | 2/444 (0.5%) | 0/444 (0%) | ||
| Diarrhea | 4/444 (0.9%) | 2/444 (0.5%) | ||
| Duodenal ulcer | 2/444 (0.5%) | 0/444 (0%) | ||
| Duodenal ulcer hemorrhage | 1/444 (0.2%) | 1/444 (0.2%) | ||
| Epigastric pain | 1/444 (0.2%) | 0/444 (0%) | ||
| Esophageal hemorrhage | 1/444 (0.2%) | 0/444 (0%) | ||
| Esophageal varices hemorrhage | 6/444 (1.4%) | 7/444 (1.6%) | ||
| Enterocolitis | 0/444 (0%) | 1/444 (0.2%) | ||
| Gastric varices bleeding | 1/444 (0.2%) | 0/444 (0%) | ||
| Gastric varices haemorrhage | 2/444 (0.5%) | 7/444 (1.6%) | ||
| Gastroduodenal ulcer | 1/444 (0.2%) | 1/444 (0.2%) | ||
| Gastroesophageal varices hemorrhage | 1/444 (0.2%) | 0/444 (0%) | ||
| Gastric perforation | 0/444 (0%) | 1/444 (0.2%) | ||
| Gastrointestinal hemorrhage | 0/444 (0%) | 2/444 (0.5%) | ||
| Incarcerated inguinal hernia | 1/444 (0.2%) | 0/444 (0%) | ||
| Inguinal hernia | 1/444 (0.2%) | 2/444 (0.5%) | ||
| Irritable bowel syndrome | 1/444 (0.2%) | 0/444 (0%) | ||
| Ischemia bowel | 1/444 (0.2%) | 0/444 (0%) | ||
| Ischemic enterocolitis | 1/444 (0.2%) | 0/444 (0%) | ||
| Large intestine polyp | 1/444 (0.2%) | 0/444 (0%) | ||
| Melaena | 1/444 (0.2%) | 0/444 (0%) | ||
| Hematemesis | 0/444 (0%) | 1/444 (0.2%) | ||
| Intestinal obstruction | 0/444 (0%) | 1/444 (0.2%) | ||
| Intra-abdominal haemorrhage | 0/444 (0%) | 1/444 (0.2%) | ||
| Mallory-Weiss syndrome | 0/444 (0%) | 1/444 (0.2%) | ||
| Mouth haemorrhage | 0/444 (0%) | 1/444 (0.2%) | ||
| Nausea | 1/444 (0.2%) | 0/444 (0%) | ||
| Oesophageal varices haemorrhage | 6/444 (1.4%) | 7/444 (1.6%) | ||
| Pancreatitis | 2/444 (0.5%) | 0/444 (0%) | ||
| Periodontal disease | 1/444 (0.2%) | 0/444 (0%) | ||
| Right upper quadrant pain | 1/444 (0.2%) | 1/444 (0.2%) | ||
| Ulcer duodenal haemorrhage | 1/444 (0.2%) | 0/444 (0%) | ||
| Upper gastrointestinal hemorrhage | 1/444 (0.2%) | 1/444 (0.2%) | ||
| Varices oesophageal | 1/444 (0.2%) | 6/444 (1.4%) | ||
| Vomiting | 3/444 (0.7%) | 0/444 (0%) | ||
| General disorders | ||||
| Condition aggravated | 1/444 (0.2%) | 0/444 (0%) | ||
| Disease progression | 2/444 (0.5%) | 0/444 (0%) | ||
| Edema limbs | 2/444 (0.5%) | 1/444 (0.2%) | ||
| Fever | 13/444 (2.9%) | 11/444 (2.5%) | ||
| Gait disturbance | 1/444 (0.2%) | 0/444 (0%) | ||
| Malaise | 3/444 (0.7%) | 0/444 (0%) | ||
| Multi organ failure | 1/444 (0.2%) | 0/444 (0%) | ||
| Pain | 1/444 (0.2%) | 0/444 (0%) | ||
| Weakness generalised | 5/444 (1.1%) | 0/444 (0%) | ||
| Fatigue | 0/444 (0%) | 2/444 (0.5%) | ||
| Hepatobiliary disorders | ||||
| Acute cholecystitis | 1/444 (0.2%) | 0/444 (0%) | ||
| Acute hepatic failure | 2/444 (0.5%) | 1/444 (0.2%) | ||
| Bile duct stenosis | 1/444 (0.2%) | 5/444 (1.1%) | ||
| Biliary fistula | 1/444 (0.2%) | 0/444 (0%) | ||
| Biloma | 5/444 (1.1%) | 1/444 (0.2%) | ||
| Cholangitis | 5/444 (1.1%) | 2/444 (0.5%) | ||
| Cholangitis acute | 1/444 (0.2%) | 2/444 (0.5%) | ||
| Cholecystitis | 3/444 (0.7%) | 4/444 (0.9%) | ||
| Dilatation intrahepatic duct acquired | 1/444 (0.2%) | 0/444 (0%) | ||
| Gallbladder perforation | 0/444 (0%) | 1/444 (0.2%) | ||
| Haemobilia | 0/444 (0%) | 2/444 (0.5%) | ||
| Hepatic failure | 16/444 (3.6%) | 11/444 (2.5%) | ||
| Hepatic function disorder | 11/444 (2.5%) | 4/444 (0.9%) | ||
| Hepatic necrosis | 1/444 (0.2%) | 1/444 (0.2%) | ||
| Hepatopathy | 0/444 (0%) | 2/444 (0.5%) | ||
| Hyperbilirubinemia | 1/444 (0.2%) | 2/444 (0.5%) | ||
| Jaundice | 1/444 (0.2%) | 2/444 (0.5%) | ||
| Obstructive jaundice | 0/444 (0%) | 1/444 (0.2%) | ||
| Portal vein thrombosis | 2/444 (0.5%) | 2/444 (0.5%) | ||
| Hepatic vein thrombosis | 1/444 (0.2%) | 0/444 (0%) | ||
| Hepatorenal syndrome | 6/444 (1.4%) | 0/444 (0%) | ||
| Appendicitis perforated | 2/444 (0.5%) | 1/444 (0.2%) | ||
| Bacteremia | 3/444 (0.7%) | 3/444 (0.7%) | ||
| Immune system disorders | ||||
| Contrast media allergy | 1/444 (0.2%) | 0/444 (0%) | ||
| Infections and infestations | ||||
| Acute bronchitis | 1/444 (0.2%) | 0/444 (0%) | ||
| Acute gastroenteritis | 2/444 (0.5%) | 0/444 (0%) | ||
| Acute pyelonephritis | 2/444 (0.5%) | 0/444 (0%) | ||
| Biliary tract infection | 1/444 (0.2%) | 3/444 (0.7%) | ||
| Bronchopneumonia | 1/444 (0.2%) | 0/444 (0%) | ||
| Cellulitis of foot | 1/444 (0.2%) | 0/444 (0%) | ||
| Cryptococcal pneumonitis | 1/444 (0.2%) | 0/444 (0%) | ||
| Cystitis | 1/444 (0.2%) | 0/444 (0%) | ||
| Enteritis infectious | 1/444 (0.2%) | 0/444 (0%) | ||
| Hepatic infection bacterial | 1/444 (0.2%) | 0/444 (0%) | ||
| Herpes zoster | 1/444 (0.2%) | 2/444 (0.5%) | ||
| Infectious colitis | 1/444 (0.2%) | 1/444 (0.2%) | ||
| Intra-abdominal infection | 3/444 (0.7%) | 0/444 (0%) | ||
| Liver abscess | 34/444 (7.7%) | 3/444 (0.7%) | ||
| Otitis media chronic | 1/444 (0.2%) | 0/444 (0%) | ||
| Periodontal abscess | 2/444 (0.5%) | 0/444 (0%) | ||
| Pneumonia | 5/444 (1.1%) | 1/444 (0.2%) | ||
| Pulpitis | 1/444 (0.2%) | 0/444 (0%) | ||
| Rectal abscess | 1/444 (0.2%) | 0/444 (0%) | ||
| Sepsis | 6/444 (1.4%) | 4/444 (0.9%) | ||
| Spontaneous bacterial peritonitis | 5/444 (1.1%) | 0/444 (0%) | ||
| Tuberculous pleurisy | 1/444 (0.2%) | 1/444 (0.2%) | ||
| UTI | 1/444 (0.2%) | 0/444 (0%) | ||
| Upper respiratory infection | 1/444 (0.2%) | 0/444 (0%) | ||
| Urinary tract infection | 1/444 (0.2%) | 2/444 (0.5%) | ||
| Pyelonephritis | 0/444 (0%) | 1/444 (0.2%) | ||
| Injury, poisoning and procedural complications | ||||
| Compression fracture | 1/444 (0.2%) | 0/444 (0%) | ||
| Fall | 1/444 (0.2%) | 1/444 (0.2%) | ||
| Fracture of lateral malleolus, closed | 2/444 (0.5%) | 3/444 (0.7%) | ||
| Humerus fracture | 1/444 (0.2%) | 1/444 (0.2%) | ||
| Maternal exposure during pregnancy | 1/444 (0.2%) | 0/444 (0%) | ||
| Nerve injury | 1/444 (0.2%) | 0/444 (0%) | ||
| Operative haemorrhage | 1/444 (0.2%) | 0/444 (0%) | ||
| Polytraumatism | 1/444 (0.2%) | 0/444 (0%) | ||
| Post embolization syndrome | 1/444 (0.2%) | 0/444 (0%) | ||
| Post procedural bile leak | 3/444 (0.7%) | 0/444 (0%) | ||
| Ankle fracture | 0/444 (0%) | 1/444 (0.2%) | ||
| Femoral neck fracture | 0/444 (0%) | 2/444 (0.5%) | ||
| Traffic accident | 0/444 (0%) | 1/444 (0.2%) | ||
| Investigations | ||||
| ALT increased | 3/444 (0.7%) | 1/444 (0.2%) | ||
| AST increased | 3/444 (0.7%) | 1/444 (0.2%) | ||
| Blood bilirubin increased | 1/444 (0.2%) | 2/444 (0.5%) | ||
| CRP increased | 2/444 (0.5%) | 0/444 (0%) | ||
| Creatinine increased | 2/444 (0.5%) | 1/444 (0.2%) | ||
| Elevated liver enzymes | 1/444 (0.2%) | 0/444 (0%) | ||
| Liver biopsy | 1/444 (0.2%) | 0/444 (0%) | ||
| Spleen scan abnormal | 1/444 (0.2%) | 0/444 (0%) | ||
| Platelet count decreased | 0/444 (0%) | 1/444 (0.2%) | ||
| WBC decreased | 0/444 (0%) | 1/444 (0.2%) | ||
| Hypokalaemia | 2/444 (0.5%) | 1/444 (0.2%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 2/444 (0.5%) | 1/444 (0.2%) | ||
| Diabetes mellitus aggravated | 1/444 (0.2%) | 2/444 (0.5%) | ||
| Electrolyte imbalance | 1/444 (0.2%) | 0/444 (0%) | ||
| Gout aggravated | 1/444 (0.2%) | 0/444 (0%) | ||
| Hypercalcaemia | 1/444 (0.2%) | 1/444 (0.2%) | ||
| Hyperglycemia | 1/444 (0.2%) | 4/444 (0.9%) | ||
| Hyperkalemia | 2/444 (0.5%) | 0/444 (0%) | ||
| Hypoglycaemia | 2/444 (0.5%) | 0/444 (0%) | ||
| Inappetence | 2/444 (0.5%) | 0/444 (0%) | ||
| Inappetence | 1/444 (0.2%) | 1/444 (0.2%) | ||
| Tumor lysis syndrome | 1/444 (0.2%) | 0/444 (0%) | ||
| Hyponatremia | 0/444 (0%) | 2/444 (0.5%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthritis | 2/444 (0.5%) | 0/444 (0%) | ||
| Back pain | 2/444 (0.5%) | 2/444 (0.5%) | ||
| Cervical disc herniation | 1/444 (0.2%) | 0/444 (0%) | ||
| Pain in thigh | 1/444 (0.2%) | 0/444 (0%) | ||
| Pseudogout | 1/444 (0.2%) | 0/444 (0%) | ||
| Rhabdomyolysis | 1/444 (0.2%) | 0/444 (0%) | ||
| Spinal column stenosis | 3/444 (0.7%) | 1/444 (0.2%) | ||
| Wrist pain | 1/444 (0.2%) | 0/444 (0%) | ||
| Avascular necrosis femoral head | 0/444 (0%) | 1/444 (0.2%) | ||
| Spondylitis | 0/444 (0%) | 1/444 (0.2%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Basal cell carcinoma | 1/444 (0.2%) | 0/444 (0%) | ||
| Bone metastases | 8/444 (1.8%) | 3/444 (0.7%) | ||
| Brain metastases | 1/444 (0.2%) | 0/444 (0%) | ||
| Cancer of descending colon | 1/444 (0.2%) | 0/444 (0%) | ||
| Gastric cancer | 2/444 (0.5%) | 2/444 (0.5%) | ||
| Hemangioma | 1/444 (0.2%) | 0/444 (0%) | ||
| Hepatocellular carcinoma non-resectable | 1/444 (0.2%) | 5/444 (1.1%) | ||
| Hepatoma recurrent | 1/444 (0.2%) | 0/444 (0%) | ||
| Liver carcinoma ruptured | 2/444 (0.5%) | 6/444 (1.4%) | ||
| Lung metastases | 2/444 (0.5%) | 0/444 (0%) | ||
| Pancreatic carcinoma | 1/444 (0.2%) | 0/444 (0%) | ||
| Spinal metastases | 1/444 (0.2%) | 0/444 (0%) | ||
| Tumor necrosis | 2/444 (0.5%) | 0/444 (0%) | ||
| Tumor rupture | 1/444 (0.2%) | 0/444 (0%) | ||
| Adenocarcinoma of the gastrooesophageal junction | 0/444 (0%) | 1/444 (0.2%) | ||
| Benign neoplasm of spinal cord | 0/444 (0%) | 1/444 (0.2%) | ||
| Bladder cancer | 0/444 (0%) | 4/444 (0.9%) | ||
| Cecal cancer | 0/444 (0%) | 1/444 (0.2%) | ||
| Inverting papilloma of the nasal cavity | 0/444 (0%) | 1/444 (0.2%) | ||
| Malignant neoplasm of cheek mucosa | 0/444 (0%) | 2/444 (0.5%) | ||
| Oesophageal carcinoma | 0/444 (0%) | 1/444 (0.2%) | ||
| Rectal cancer | 0/444 (0%) | 1/444 (0.2%) | ||
| Schwannoma | 0/444 (0%) | 1/444 (0.2%) | ||
| Tumour embolism | 0/444 (0%) | 1/444 (0.2%) | ||
| Nervous system disorders | ||||
| Cerebral infarction | 5/444 (1.1%) | 5/444 (1.1%) | ||
| Hepatic encephalopathy | 12/444 (2.7%) | 6/444 (1.4%) | ||
| Intracranial hemorrhage | 3/444 (0.7%) | 1/444 (0.2%) | ||
| Numbness of lower extremities | 1/444 (0.2%) | 0/444 (0%) | ||
| Spinal cord compression | 1/444 (0.2%) | 0/444 (0%) | ||
| Syncope | 1/444 (0.2%) | 0/444 (0%) | ||
| Dizziness | 0/444 (0%) | 1/444 (0.2%) | ||
| Psychiatric disorders | ||||
| Delirium | 1/444 (0.2%) | 0/444 (0%) | ||
| Orientation disturbed | 1/444 (0.2%) | 0/444 (0%) | ||
| Renal and urinary disorders | ||||
| Acute kidney injury | 4/444 (0.9%) | 3/444 (0.7%) | ||
| Renal failure | 4/444 (0.9%) | 4/444 (0.9%) | ||
| Reproductive system and breast disorders | ||||
| Benign prostatic hyperplasia | 0/444 (0%) | 1/444 (0.2%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Asphyxia | 1/444 (0.2%) | 0/444 (0%) | ||
| Aspiration pneumonitis | 2/444 (0.5%) | 0/444 (0%) | ||
| Bronchiectasis | 1/444 (0.2%) | 0/444 (0%) | ||
| COPD exacerbation | 1/444 (0.2%) | 0/444 (0%) | ||
| Chronic cough | 2/444 (0.5%) | 1/444 (0.2%) | ||
| Dyspnea | 2/444 (0.5%) | 0/444 (0%) | ||
| Pleural effusion | 7/444 (1.6%) | 2/444 (0.5%) | ||
| Pneumonitis | 1/444 (0.2%) | 0/444 (0%) | ||
| Pulmonary embolism | 1/444 (0.2%) | 1/444 (0.2%) | ||
| Respiratory failure | 1/444 (0.2%) | 0/444 (0%) | ||
| Shortness of breath | 1/444 (0.2%) | 0/444 (0%) | ||
| Asthma | 0/444 (0%) | 1/444 (0.2%) | ||
| Atelectasis | 0/444 (0%) | 1/444 (0.2%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Eczema nummular | 1/444 (0.2%) | 0/444 (0%) | ||
| Stevens-Johnson syndrome | 0/444 (0%) | 1/444 (0.2%) | ||
| Surgical and medical procedures | ||||
| Gastrooesophageal variceal haemorrhage prophylaxis | 3/444 (0.7%) | 0/444 (0%) | ||
| Induced abortion | 1/444 (0.2%) | 0/444 (0%) | ||
| Oesophageal variceal ligation | 3/444 (0.7%) | 5/444 (1.1%) | ||
| Vascular disorders | ||||
| Varicose vein ruptured | 1/444 (0.2%) | 0/444 (0%) | ||
| Abdominal aortic aneurysm | 0/444 (0%) | 1/444 (0.2%) | ||
| Arterial stenosis | 0/444 (0%) | 1/444 (0.2%) | ||
| Deep vein thrombosis | 0/444 (0%) | 1/444 (0.2%) | ||
| Obstructive arteriosclerosis of lower extremities | 0/444 (0%) | 1/444 (0.2%) | ||
| Vascular disorder | 0/444 (0%) | 1/444 (0.2%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Orantinib | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 443/444 (99.8%) | 436/444 (98.2%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 54/444 (12.2%) | 32/444 (7.2%) | ||
| Gastrointestinal disorders | ||||
| Abdominal distension | 50/444 (11.3%) | 53/444 (11.9%) | ||
| Abdominal pain | 317/444 (71.4%) | 292/444 (65.8%) | ||
| Abdominal pain upper | 56/444 (12.6%) | 46/444 (10.4%) | ||
| Ascites | 140/444 (31.5%) | 73/444 (16.4%) | ||
| Constipation | 179/444 (40.3%) | 147/444 (33.1%) | ||
| Diarrhoea | 123/444 (27.7%) | 70/444 (15.8%) | ||
| Dyspepsia | 51/444 (11.5%) | 47/444 (10.6%) | ||
| Gastritis | 23/444 (5.2%) | 29/444 (6.5%) | ||
| Gastrointestinal pain | 22/444 (5%) | 14/444 (3.2%) | ||
| Nausea | 179/444 (40.3%) | 179/444 (40.3%) | ||
| Vomiting | 126/444 (28.4%) | 116/444 (26.1%) | ||
| General disorders | ||||
| Chills | 34/444 (7.7%) | 23/444 (5.2%) | ||
| Face oedema | 138/444 (31.1%) | 8/444 (1.8%) | ||
| Fatigue | 101/444 (22.7%) | 92/444 (20.7%) | ||
| Malaise | 101/444 (22.7%) | 86/444 (19.4%) | ||
| Non-cardiac chest pain | 32/444 (7.2%) | 25/444 (5.6%) | ||
| Oedema peripheral | 130/444 (29.3%) | 59/444 (13.3%) | ||
| Pyrexia | 264/444 (59.5%) | 284/444 (64%) | ||
| Hepatobiliary disorders | ||||
| Hepatic failure | 24/444 (5.4%) | 20/444 (4.5%) | ||
| Infections and infestations | ||||
| Liver abscess | 30/444 (6.8%) | 3/444 (0.7%) | ||
| Upper respiratory tract infection | 86/444 (19.4%) | 85/444 (19.1%) | ||
| Investigations | ||||
| ALT increased | 200/444 (45%) | 170/444 (38.3%) | ||
| AST increased | 223/444 (50.2%) | 189/444 (42.6%) | ||
| ALP increased | 64/444 (14.4%) | 22/444 (5%) | ||
| Bilirubin increased | 77/444 (17.3%) | 75/444 (16.9%) | ||
| CRP increased | 47/444 (10.6%) | 44/444 (9.9%) | ||
| Lymphocyte count decreased | 40/444 (9%) | 45/444 (10.1%) | ||
| Platelet count decreased | 53/444 (11.9%) | 48/444 (10.8%) | ||
| Weight decreased | 31/444 (7%) | 20/444 (4.5%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 209/444 (47.1%) | 149/444 (33.6%) | ||
| Hyperkalaemia | 23/444 (5.2%) | 14/444 (3.2%) | ||
| Hypoalbuminaemia | 98/444 (22.1%) | 85/444 (19.1%) | ||
| Hypokalaemia | 34/444 (7.7%) | 16/444 (3.6%) | ||
| Hyponatraemia | 31/444 (7%) | 22/444 (5%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 34/444 (7.7%) | 19/444 (4.3%) | ||
| Back pain | 90/444 (20.3%) | 94/444 (21.2%) | ||
| Musculoskeletal pain | 38/444 (8.6%) | 36/444 (8.1%) | ||
| Myalgia | 32/444 (7.2%) | 22/444 (5%) | ||
| Pain in extremity | 40/444 (9%) | 30/444 (6.8%) | ||
| Nervous system disorders | ||||
| Dizziness | 38/444 (8.6%) | 35/444 (7.9%) | ||
| Headache | 74/444 (16.7%) | 62/444 (14%) | ||
| Psychiatric disorders | ||||
| Insomnia | 79/444 (17.8%) | 68/444 (15.3%) | ||
| Renal and urinary disorders | ||||
| Chromaturia | 103/444 (23.2%) | 18/444 (4.1%) | ||
| Proteinuria | 47/444 (10.6%) | 17/444 (3.8%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 69/444 (15.5%) | 68/444 (15.3%) | ||
| Dyspnoea | 29/444 (6.5%) | 30/444 (6.8%) | ||
| Pleural effusion | 36/444 (8.1%) | 16/444 (3.6%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 43/444 (9.7%) | 51/444 (11.5%) | ||
| Vascular disorders | ||||
| Hypertension | 59/444 (13.3%) | 57/444 (12.8%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Taiho Pharmaceutical Co., Ltd. |
|---|---|
| Organization | Clinical Trial Registration Contact |
| Phone | |
| toiawase@taiho.co.jp |
Responsible Party:
Taiho Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01465464
Other Study ID Numbers:
- Taiho132150
First Posted:
Nov 4, 2011
Last Update Posted:
Aug 7, 2019
Last Verified:
Aug 1, 2019